The most common method to treat anterior segment diseases of the eye is by topical drop administration due to its low cost, ease of application, and non-invasiveness. Unfortunately, numerous barriers prevent efficient delivery of therapeutics to the anterior segment resulting in less than 5% of the administered dose reaching the anterior tissues in most cases. Static barriers including tight junctions of the conjunctiva, the hydrophobic corneal epithelium and hydrophilic corneal stroma, and dynamic barriers including the rapid tear turnover, and the vasculature and lymphatics of the conjunctiva all contribute to the highly impenetrable anterior surface. Pre-corneal clearance mechanisms such as blinking, rapid tear turnover, and lacrimal drainage are additional barriers even before reaching the anterior tissues that must be overcome. Upon instillation of an eye drop, the maximal 30 μL that can be held in the cul-de-sac is restored to its normal 7 μL tear volume within 2 to 3 minutes resulting in the rapid drainage of 80% or more of the drug through the nasolacrimal duct for systemic absorption and potential side effects.
The tear film itself is composed of an outer lipid layer, a middle aqueous layer containing secreted mucin, and an inner mucin layer immobilized on the glycocalyx covering the corneal and conjunctival epithelium. The inner immobilized mucin layer is thought to act as yet another protective barrier against the diffusion of macromolecules, microbes, and hydrophobic molecules due to its hydrophilic nature. Rose bengal, an anionic dye has been shown to stain corneal epithelium more readily with less mucin showing that mucin has an effect on drug delivery.
One method that has been explored to improve drug transport into ocular tissues has been to utilize mucoadhesive polymers that increase the bioavailability of drug in the immobilized mucin layer. There are many well-known natural mucoadhesive polymers including chitosan, cellulose derivatives, thiomers, and many others, but these materials generally lack the versatility for nanoparticle design to achieve desirable release characteristics. Phenylboronic acid (PBA) is a synthetic molecule that has been extensively used in glucose sensing and insulin delivery systems due to its ability to form high affinity complexes with 1,2-cis-diols. This affinity between boronic acids and diols has also been utilized in other mucoadhesive drug delivery systems such as vaginal delivery of interferon, nasal delivery of insulin, and ocular delivery of cyclosporine A (CycA).
It would be desirable to develop novel methods of delivering cargo, such as therapeutic agents, to mucosal surfaces, including the ocular mucosa.